CA-125 Levels Are Predictive of Survival in Low-Grade Serous Ovarian Cancer-A Multicenter Analysis

Christoph Wohlmuth; Vladimir Djedovic; Susanne K Kjaer; Allan Jensen; Rosalind Glasspool; Patricia Roxburgh; Anna DeFazio; Sharon E Johnatty; Penelope M Webb; Francesmary Modugno; Diether Lambrechts; Joellen M Schildkraut; Andrew Berchuck; Liv Cecilie Vestrheim Thomsen; Line Bjorge; Estrid Høgdall; Claus K Høgdall; Ellen L Goode; Stacey J Winham; Keitaro Matsuo; Beth Y Karlan; Jenny Lester; Marc T Goodman; Pamela J Thompson; Tanja Pejovic; Marjorie J Riggan; Katherine Lajkosz; Alicia Tone; Taymaa May

doi:10.3390/cancers14081954

CA-125 Levels Are Predictive of Survival in Low-Grade Serous Ovarian Cancer-A Multicenter Analysis

Cancers (Basel). 2022 Apr 13;14(8):1954. doi: 10.3390/cancers14081954.

Authors

Christoph Wohlmuth^{1

2}, Vladimir Djedovic^{1

3}, Susanne K Kjaer^{4

5}, Allan Jensen⁴, Rosalind Glasspool^{6

7}, Patricia Roxburgh^{6

7}, Anna DeFazio^{8

9

10

11}, Sharon E Johnatty¹², Penelope M Webb¹³, Francesmary Modugno^{14

15}, Diether Lambrechts^{16

17}, Joellen M Schildkraut¹⁸, Andrew Berchuck¹⁹, Liv Cecilie Vestrheim Thomsen^{20

21}, Line Bjorge^{20

21}, Estrid Høgdall²², Claus K Høgdall⁵, Ellen L Goode²³, Stacey J Winham²⁴, Keitaro Matsuo^{25

26}, Beth Y Karlan²⁷, Jenny Lester²⁷, Marc T Goodman²⁸, Pamela J Thompson²⁹, Tanja Pejovic^{30

31}, Marjorie J Riggan¹⁹, Katherine Lajkosz³², Alicia Tone¹, Taymaa May¹

Affiliations

¹ Division of Gynecologic Oncology, Princess Margaret Hospital, University Health Network, Toronto, ON M5G 2M9, Canada.
² Department of Obstetrics and Gynecology, Paracelsus Medical University, 5020 Salzburg, Austria.
³ Department of Internal Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
⁴ Department of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
⁵ Department of Gynaecology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark.
⁶ Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow G12 0YN, UK.
⁷ Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.
⁸ Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, NSW 2145, Australia.
⁹ Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW 2145, Australia.
¹⁰ The Daffodil Centre, a Joint Venture with Cancer Council NSW, The Daffodil Centre, The University of Sydney, Sydney, NSW 2145, Australia.
¹¹ Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Center, Melbourne, VIC 3000, Australia.
¹² Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
¹³ Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
¹⁴ Women's Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, PA 15213, USA.
¹⁵ Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
¹⁶ Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
¹⁷ VIB Center for Cancer Biology, VIB, 3000 Leuven, Belgium.
¹⁸ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
¹⁹ Department of Gynecologic Oncology, Duke University Hospital, Durham, NC 27710, USA.
²⁰ Department of Obstetrics and Gynecology, Haukeland University Hospital, 5021 Bergen, Norway.
²¹ Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.
²² Department of Pathology, Herlev Hospital, University of Copenhagen, DK-2100 Copenhagen, Denmark.
²³ Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.
²⁴ Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.
²⁵ Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
²⁶ Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
²⁷ Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
²⁸ Cancer Prevention and Control Program, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
²⁹ Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
³⁰ Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA.
³¹ Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
³² Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G 2C1, Canada.

Abstract

Objective: Studies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC.

Methods: Women with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated.

Results: A total of 176 women with LGSC were included in this study; 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99; 95%CI, 0.96-1.01 and 0.98; 95%CI 0.95-1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43-12.73) and OS (HR 1.69, 95%CI 0.56-5.05). Elevated CA-125 (≥35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (≥35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36-5.81) and OS (HR 6.62, 95%CI 2.45-17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85).

Conclusion: Advanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS.

Highlights: 1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival.

Keywords: CA-125; low-grade serous cancer; ovarian cancer; survival.

Abstract

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